Robert Clancy

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Robert Clancy

Associate Professor, Department of Medicine
Medicine

Contact Info

Address
301 East 17th Street
New York, NY 10003

212/263-0751
Robert.Clancy@nyumc.org

Research Summary

The interaction between the extracellular matrix and cells affects a wide spectrum of cellular processes including migration, growth, death, capacity to degrade matrix, capacity to synthesize matrix, differentiation, and cell attachment. In human neutrophils, we study signalling by beta1 integrin receptors which contribute to cell attachment and migration. Additionally, we study the effect of nitric oxide, an inflammatory mediator, on the signalling pathways. Neutrophils help destroy foreign invaders at tissue sites but first must reversibly undergo cell attachment through the endothelium and matrix. We hypothesize that nitric oxide modulates matrix-cell interaction by the reversible inhibition of neutrophil attachment to fibronectin (ligand for beta1 integrin)-coated surfaces. We recently showed that nitric oxide inhibits adherence associated with a stimulation of actin-ADP ribosylation. In bovine chondrocytes, we study signalling by beta1 integrin receptors which contribute to the capacity to degrade matrix and differentiation. We hypothesize that nitric oxide, a mediator of arthritis, inhibits chondrocyte adherence and cell capacity to contribute to matrix synthesis and breakdown. Recently, we studied signalling by beta1 integrins in chondrocytes by measuring protein accumulation to contact sites in chondrocytes exposed to fibronectin-coated and albumin-coated beads. Chondrocytes exposed to albumin-coated beads failed to generate a response, but cytoskeletal and signalling molecules accumulated to fibronectin-coated and albumin-coated beads which include polymerized actin, focal adhesion kinase, and the accumulation of tyrosine phosphorylated proteins (see Figure). Prior treatment of chondrocytes with catabolic cytokines (which stimulate nitric oxide synthesis) prevent the response. Collectively, our results suggest that nitric oxide induced a persistently altered chondrocyte phenotype (chondrocytes incapable of signalling via beta 1 integrins) which might be reversed or prevented by using nitric oxide antagonists. A persistently altered state in chondrocytes would greatly change the ability of such chondrocytes to mature and perhaps result in the changes seen in arthritis.

Research Interests

Molecular Mechanism of beta1 Integrin Signal Transduction

Endosomal Toll-like receptors in clinically overt and silent autoimmunity
Clancy, Robert M; Markham, Androo J; Buyon, Jill P. Endosomal Toll-like receptors in clinically overt and silent autoimmunity. Immunological reviews. 2016 Jan;269(1):76-84 (1878232)

HLA associations in mothers of children with cardiac manifestations of neonatal lupus
Ainsworth, H C; Langefeld, C D; Marion, M C; Costedoat-Chalumeau, N; Brucato, A; Buyon, J P; Clancy, R M. HLA associations in mothers of children with cardiac manifestations of neonatal lupus [Meeting Abstract]. Arthritis & rheumatology. 2015 October 2015;67:- (1904212)

Heritable endotheliopathy and apolipoproteinl1 risk traits in SLE
Blazer, A; Markham, A; Rasmussen, S; Buyon, J P; Belmont, H M; Mehta-Lee, S; Nwaukoni, J; Izmirly, P M; Clancy, R. Heritable endotheliopathy and apolipoproteinl1 risk traits in SLE [Meeting Abstract]. Arthritis & rheumatology. 2015 October 2015;67:- (1904432)

Single cell sequencing of non-lesional non-sun exposed skin from SLE patients with proteinuria supports widespread endothelial activation
Clancy, R; Der, E; Akat, K; Broder, A R; Belmont, H M; Izmirly, P M; Goilav, B; Tuschl, T; Putterman, C; Buyon, J P. Single cell sequencing of non-lesional non-sun exposed skin from SLE patients with proteinuria supports widespread endothelial activation [Meeting Abstract]. Arthritis & rheumatology. 2015 October 2015;67:- (1904382)

Platelet activation and endothelial reactivity in the pathogenesis of tissue inflammation/injury in systemic lupus erythematosus
Clancy, R; Nhek, S; Newman, J; Nwaukoni, J; Rasmussen, S; Buyon, J P; Rubin, M; Lee, K; Berger, J. Platelet activation and endothelial reactivity in the pathogenesis of tissue inflammation/injury in systemic lupus erythematosus [Meeting Abstract]. Arthritis & rheumatology. 2015 October 2015;67:- (1903942)